Synthesis of substituted cyclooctatetraenes



United States Patent SYNTHESIS OF SUBSTITUTED CYCLO- OCTATETRAENES Arthur C. Cope, Belmont, and Mark R. Kinter, Cambridge, Mass., assignors, by mesne assignments, to the United States of America as represented by the Secretary of the Navy No Drawing. Application January 19, 1951, Serial No. 206,924

8 Claims. (Cl. 260-668) This invention relates to a process for the preparation of substituted cyclooctatetraenes from cyclooctatetraene, and, more particularly, for the preparation of arylcyclooctatetraenes from the reaction of cyclooctatetraene with organometallic compounds by addition followed by a process equivalent to the hydrogen transfer between the initial adduct and cyclo'cictatetraene.

The properties of substituted cycloiictatetraenes are of considerable interest inasmuch as the structure is a symmetrical cyclic system of alternate double and single bonds possessing greater reactive ability than the stable benzene ring. Substituted cyclooctatetraenes appear to be useful chemical intermediates and to possess ultraviolet absorption spectra suitable as ultraviolet screening agents. Cyclooctatetraene has been prepared by the polymerization of acetylene and by a number of complex methods, notably by synthesis from pseudopelletierine by degrading through methylgranatanine to cyclooctadiene and dehydrogenating to cyclooctatetraene.

Organolithiurn compounds are known to add to the carhon-carbon double bonds of aryl-substituted olefins and fulvenes and to conjugated dienes in the initiation of polymerization. The occurrence of the above addition reactions suggested the possibility of treating cyclooctatetraene with an organometallic compound, such as phenyllithium, to obtain substituted cyclooctatrienes as possible intermediates in the synthesis of substituted cyclodctatetraenes. It was found, however, that the reaction led directly to substituted cyclo'tictatetraenes as well as to cycloijctatrienes.

V For example, phenyllithiurn is found to react slowly with cyclooctatetraene in ether solution in an inert atmosphere, or more rapidly if the ether is distilled and the mixture heated at 90 centigrade, to give a mixture of phenylcyclooctatetraene and organolithium compounds which are decomposed by hydrolysis. Distillation of the decomposition products yields a low boiling fraction containing cyclooctatrienes and recovered cyclooctatetraene and a high boiling fraction containing principally the phenylcyclooctatetraene and phenylcyclooctatriene. The phenylcyclooctatetraene may be purified by conversion into a crystalline 1:1 complex with silver nitrate from which the hydrocarbon is regenerated by treatment with ammonium hydroxide or aqueous sodium chloride. The recovery of cyclooctatetraene from the low boiling fraction may be carried out by extraction with silver nitrate.

' Additional information regarding the reaction of phenyllithium with cyclooctatetraene is obtainable by decomposing the intermediate organolithium compounds by carbonation rather than by hydrolysis. The amount of phenylcyclooctatetraene in the product is found to be unchanged but the low boiling fraction does not contain cyclooctatrienes, instead an acid, which readily polymerizes, is found.

Zfiiilid? Patented Aug. 9, 1955 Accordingly, the following reactions occur when cyclooctatetraene is treated with phenyllithium:

I CBHiLl I (or the 1,2-adduct) L H i Phenylcyclotictatetraene Hydrolysis of the organolithium compounds found in Reactions 1 and 2 yield:

Phenylcycloiictatriene 1,3,6-cycloiictatriene 1,3,5-cycl06ctatriene The yield of phenylcyclooctatetraene is found to be the range of 14-26%.

Extension of the synthesis of substituted cyclooctatetraenes by reaction of cyclooctatetraene with other organoalkalimetallic compounds yields products consistent with the results indicated for the phenyllithium Equations 1 and 2. Thus, reaction of cyclooctatetraene with p-dimethylaminophenyllithium yields p-dirnethylaminophenylcyclooctatetraene and a mixture of cyclooctatrienes with recovered cyclooctatetraene. Phenylsodium reacts similarly with cyclooctatetraene, yielding phenycyclootatetraene and cyclofjctatrienes.

To carry out the reaction of phenyllithium with cyclooctatetraene the following procedure has been found effective on a laboratory scale:

A dry one-liter three-necked flask was equipped with a mechanical stirrer, a dropping funnel and a reflux conwas heated under reflux for an additional period of one hour. 104 grams (1.0 mole) of cyclooctatetraene was added, and the reflux condenser was replaced by a 20 x 1.5 centimeter Vigreux column. The mixture was heated gradually to a bath temperature of 90 centigrade during one hour, While most of the ether distilled, and then was stirred at that temperature for two hours. The product, an orange colored mixture containing organolithium compounds, was cooled in ice, and the dry ether which i had been removed by distillation was returned to the flask. 500 milliliters of water was added slowly with stirring to decompose the organolithium compounds by hydrolysis, and the red ether layer was separated, Washed three times with water, and dried over magnesium sulphate. Two distillations of the low boiling fraction through a x 1.5 centimeter helix-packed column separated the ether solvent and benzene formed by hydrolysis of phenyllithium from the product (72.9 grams having a boiling point 74-79 centigrade at 97 mm. of mercury pressure r1 5 1.5295). Distillation of the residue through a fractionating column separated 37.3 grams of a high boiling fraction (boiling point 9495 centigrade at 0.3 mm. of mercury pressure, 11 1.6168) containing a mixture of phenylcyclooctatetraene and phenylcyclooctatriene.

Phenylcyclooctatetraene was isolated as the silver nitrate complex by treating a solution of the high boiling fraction in 300 milliliters boiling absolute ethanol with 35.2 grams finely powdered silver nitrate. After heating for ten minutes, all of thesilver nitrate dissolved forming a yellow-green solution, and on cooling to 0 centigrade a yellow-green, crystalline silver nitrate complex separated. The crystals were collected on a filter, washed with two milliliter portions of cold ether, and air dried for one-half hour. The silver nitrate complex was decomposed by shaking with a solution of 100 milliliters of concentrated ammonium hydroxide in 100 milliliters of water. The orange liquid which was formed was extracted with two 50 milliliter portions of ether and the combined extracts were washed with water, dried over magnesium sulphate, and concentrated. Distillation through a fractionating column yielded 22.6 grams of phenylcyclooctatetraene as an orange liquid having a boiling point of 94-95" centigrade at 0.3 mm. mercury pressure, n 1.6181, @1 1.0335.

Phenylcyclooctatriene was isolated from the alcohol filtrate and ether washings which were separated from the phenylcyclooctatetraene-silver nitrate complex. The solution was concentrated under reduced pressure to a volume of 50 milliliters and shaken with 50 milliliters of concentrated ammonium hydroxide and 50 milliliters of water. The oil which separated was extracted with two 25 milliliter portions of pentane, and the combined extracts were washed with water and then extracted with six 25 milliliter portions of 50% aqueous silver nitrate. Treatment of the extracts with ammonium hydroxide caused the separation of a small additional amount of slightly impure phenylcyclooctatetraene, which after extraction and distillation yielded 1.6 grams of product. The pentane solution remaining after extraction with silver nitrate was washed with water, concentrated and the residue was distilled through a fractionating column. Approximately 1 gram of biphenyl was separated as a first fraction, followed by three fractions of phenylcyclooctatriene totaling 8.52 grams having a boiling point of 9092 centigrade at 0.3 mm. mercury pressure, r1 l.61001.6174.

The low boiling fraction (72.9 grams) yielded 1% bromobe'nzene, 26% cyclooctatrienes, and 73% cyclooctatetraene. The cyclotictatetraene was separated by extracting a solution of the fraction in 70 milliliters of pentane with nine 100 milliliter portions of 20% aqueous silver nitrate, which was the minimum amount that removed the yellow color from the pentane solution. Water was. added when necessary during the extractions to dissolve any solid cyclooctatetraene-silver nitrate complex. The silver nitrate extracts were added to 300 milliliters of concentrated ammonium hydroxide, and the yellow cyclooctatetraene, which separated, was extracted with ether and distilled through a 20 x 1.5 centimeter hel x-packed column to recover 52.1 grams of cyclooctatetraene. The colorless pentane solution was washed with water, dried over magnesium sulphate, and the pentane distilled through the helix-packed column. The residue was distilled through a fractionating column and yielded 10.5 grams of a mixture of cyclooctatrienes, having boiling point 74-78 centigrade at 93 mm. mercury pressure and n 1.5158. The ultraviolet absorption spectrum of this fraction indicated that it was a mixture of 1,3,5- and 1,3,6-cyclo6ctatrienes. The mixture of atmosphere for two hours in a solution of potassium t-butoxide in t-butyl alcohol to isomerize the 1,3,6-cyclooctatriene to 1,3,5-cyclo6ctatriene.

Alternately the organolithium compounds present in the reaction mixture obtained by heating phenyllithium and cyclooctatetraene may be carbonated rather than decomposed by hydrolysis. The reaction mixture was cooled in an ice bath, diluted with 50 milliliters of dry ether, and forced onto several hundred grams of finely powdered solid carbon dioxide. The transfer was completed by rinsing the reaction flask with two 50 milliliter portions of dry ether. After volatilization of the carbon dioxide, 200 milliliters of water and enough sodium hydroxide to make the mixture definitely basic to litmus were added. The ethereal layer was. separated, washed with water, dried over magnesium sulphate and the ether distilled through a 20 x 1.5 centimeter helix-packed column. Distillation of the residue through a fractionating column gave a low boiling fraction and a high boiling fraction.

Redistillation of the low boiling fraction yielded cyclot'jctatetraene, 42.7% recovery of the original amount of cyclooctatetraene. Treatment of the high boiling fraction as before with a silver nitrate ethanol solution yielded phenylcyclooctatetraene.

The results of the carbonation reaction indicated that the amount of phenylcyclooctatetraene in the product was unchanged but the low boiling hydrocarbon fraction contained practically no cyclooctatriene. However, the acid products obtained by acidification of the alkaline aqueous extract of the reaction mixture after carbonation tended to polymerize.

The identities of the products of the process can be confirmed according to the following procedures:

Phenylcyclooctatetraene may be characterized by quantitative hydrogenation in methanol in the presence of a palladium catalyst, requiring four molar equivalents of hydrogen, to form phenylcyclooctane; by reaction with maleic anhydride in benzene to form a colorless adduct; by reaction with p-benzoquinone to form a yellow adduct; by formation of yellow-green complex with silver nitrate, and by its ultraviolet and infrared absorption spectra.

Phenylcyclooctatriene may be characterized by the absorption of three molar equivalents to form phenylcyclooctane and by comparison of infrared and ultraviolet spectra with the spectra of an authentic sample.

The nature of the mixture of cyclooctatrienes may be determined by infrared and ultraviolet spectra, and by the maleic anhydride adduct after converting the mixture of 1,3,6- and 1,3,5-cyclooctatrienes to 1,3,5-cyclooctatriene by treatment with potassium t-butoxide.

The recovered cyclooctatetraene may be isolated and characterized by the formation of its silver nitrate complex.

As indicated previously, p-dimethylaminophenyllithium reacts with cyclooctatetraene to form an organolithium complex from which p-dimethylaminophenylcyclooctatetraene may be derived. On a laboratory scale, a solution of p-dimethylaminophenyllithium was prepared from 20 grams (0.1 mole) of recrystallized p-bromodirnethylaniline and 1.54 (0.22 gram atom) of lithium in milliliters of dry ether in an atmosphere of nitrogen (as described by Gilman et al., Journal of the American Chemical Society, volume 55, page 1252, 1933). After the preparation of the organolithium compound, 20.8 grams (0.20 mole) of cycloo'ctatetraene was added, and the mixture was gradually heated to centigrade during forty-five minutes as the ether distilled. Stirring and heating continued at the reaction temperature of 90 centigrade for a period of two hours, after which the mixture was cooled in ice and 50 milliliters of ether was added, followed by milliliters of water which was added with cooling and stirring. The red other layer was separated and combined with a 25 milliliter ethereal extract of the aqueous layer. The other solution was washed with water, and then was extracted with four 50 milliliter portions of 4% hydrochloric acid to separate basic products. The ethereal solution was washed once with water and the combined aqueous and acid extracts were made basic with aqueous sodium hydroxide. The red liquid which separated was extracted with three milliliter portions of ether, and the combined extracts were washed three times with water, dried over magnesium sulphate, and concentrated. The red liquid residue was distilled through a fractionating column to separate 4.5 grams of N,N-dimethylaniline from a high boiling residue. The residue was distilled in a short-path still at 0.4 mm. mercury pressure with a heating block temperature of 200 centigrade. The red liquid distillate solidified rapidly, yielding as an orange solid, 8.2 grams of p-dimethylaminophenylcyclooctatetraene. The crude product was recrystallized twice from hot methanol as 5.9 grams of small orange leaflets having a melting point of 89.5-90.7 centigrade.

The ethereal solution containing reaction products not extracted by 4% hydrochloric acid were concentrated and the residue distilled through a fractionating column, yielding 14.4 grams of liquid having a boiling point of 7679 centigrade at 92 mm. mercury pressure. Extraction of a solution of this material in 25 milliliters of pentane with seven 25 milliliter portions of 20% aqueous silver nitrate by the procedure described above separated 8.7 grams of recovered cyclooctatetraene and 3.83 grams of a mixture of cyclotictatrienes, which were treated with potassium t-butoxide in t-butyl alcohol to yield 3.33 grams of 1,3,5-cyclo6ctatriene.

The general utility of this method for the preparation of substituted cyclooctatetraenes by the reaction of cyclooctatetraene with organoalkalimetallic compounds is illustrated by the reaction of cyclooctatetraene with phenylsodium. As carried out on a laboratory scale, phenylsodium was prepared by adding 11.2 grams of chlorobenzene to 5.75 grams of powdered sodium and 75 milliliters of dry benzene in an atmosphere of nitrogen by a process based on the one described by Gilman et al. in Journal of the American Chemical Society, volume 62, page 1517, 1940, in which toluene was used as a solvent. 20.8 grams of cyclooctatetraene was added and the mixture was stirred and heated under reflux for one hour, and then was cooled in ice while 50 milliliters of ethanol were added, followed by 75 milliliters of water. Dilute hydrochloric acid was added until the mixture was neutral, and the benzene layer was separated. The aqueous layer was extracted with 50 milliliters of ether, and the combined benzene and ethereal solutions were washed twice with water and dried over magnesium sulphate. The solvent was distilled through a 20 x 1.5 centimeter helix-packed column, and the products were fractionated through a fractionating column. The low and high boiling fractions were separated into their components by treatment with silver nitrate by procedures similar to those described for separating the products formed in the reaction of phenyllithium and cycloiictatetraene.

The low boiling fraction yielded recovery of 6.7 grams of cyclooctatetraene and 2.44 grams of a mixture of cyclooctatrienes. The high boiling fraction of 5.43 grams yielded 3.95 grams of phenylcyclotictatetraene.

The reaction of organoalkalimetallic compounds with cyclooctatetraene is shown to proceed by addition, followed by a process equivalent to the transfer of the metal hydride from the addition compound to another molecule of cycloiictatetraene. The process also discloses methods of isolating the reaction products.

While in the foregoing disclosure the present invention has been described with respect to certain specific processes, it will be understood that one skilled in the art, without departing from the spirit of the invention, may employ various processes.

What is claimed is:

1. The method of preparing phenylcyclooctatetraene which comprises heating cyclo'octat'etraene in a solution of a reactant of the formula RM in which R is the phenyl radical and M is a member of the group consisting of lithium and sodium in an inert atmosphere to obtain a mixture of phenylcycloiictatetraene and organometallic complexes, cooling the reaction products, decomposing the complexes so formed by hydrolysis, and separating the phenylcyclooctatetraene from the other reaction products.

2. The method of preparing phenylcyclooctatetraene which comprises heating cyclo'cictatetraene in a solution of a reactant of the formula RM in which R is the phenyl radical and M is a member of the group consisting of lithium and sodium in an inert atmosphere to obtain a mixture of phenylcyclooctatetraene and organometallic complexes, cooling the reaction products, decomposing the organometallic complexes so formed by hydrolysis, and separating the phenylcyclooctatetraene from the reaction products by fractionation under reduced pressure to remove a low boiling fraction and the solvent from a high boiling residue, isolation of a crystalline complex from the high boiling residue with silver nitrate, and regeneration with ammonium hydroxide.

3. The method of preparing phenylcyclooctatetraene which comprises heating cyclooctatetraene in a solution of a reactant of the formula RM in which R is the phenyl radical and M is a member of the group consisting of lithium and sodium in an inert atmosphere to obtain a mixture of phenylcyclooctatetraene and organometallic complexes, cooling the reaction products, decomposing the complexes so formed by carbonation, and separating the phenylcyclooctatetraene from the other reaction products.

4. The method of preparing phenylcyclooctatetraene which comprises heating cyclooctatetraene in a solution of a reactant of the formula RM in which R is the phenyl radical and M is a member of the group consisting of lithium and sodium in an inert atmosphere to obtain a mixture of phenylcyclooctatetraene and organometallic complexes, cooling the reaction products, decomposing the complexes so formed by carbonation, and separating the phenylcyclooctatetraene from the other reaction products by fractionation under reduced pressure to remove a low boiling fraction and the solvent from a high boiling residue, isolation of a crystalline complex from the high boiling residue with silver nitrate and regeneration with ammonium hydroxide.

5. The method of preparing phenylcyclooctatetrane which comprises heating cyclooctatetraene in an ether solution of phenyllithium in a nitrogen atmosphere at centigrade for a period of one to two hours to form a mixture of pheuylcyclooctatetraene and organolithium complexes, cooling the reaction products in ice, decomposing the complexes so formed by hydrolysis, separating the reaction products by distillation under reduced pressure into a low boiling fraction and a high boiling residue, and isolating the phenylcyclooctatetraene from the high boiling residue as a yellow-green crystalline phenylcyclooctatetraene-silver nitrate complex, and regenerating phenylcyclooctatetraene from the silver nitrate complex by treatment with ammonium hydroxide.

6. The method of preparing phenylcyclooctatetraene which comprises heating cyclooctatetraene in a benzene solution of phenylsodium in a nitrogen atmosphere at 90 centigrade for a period of one to two hours to form a mixture of phenylcyclooctatetraene and organosodium complexes, cooling the reaction products in ice, decomposing the complexes so formed by hydrolysis, separating the reaction products by distillation under reduced pressure into a low boiling fraction and a high boiling residue, and isolating the phenylcyclooctatetraene from the high boiling residue as a yellow-green crystalline phenylcyclooctatetraene-silver nitrate complex, and regenerating phenylcyclooctatetraene from the silver nitrate complex by treatment with ammonium hydroxide.

7. The method of preparing a substituted phenylcyclo- 7 8 fictatetraene which comprises heating cyclooctatetraene stituted phenylcyclooctatetraene from the other reaction in a solution of a reactant of the formula RM, in which products. R is a substituted phenyl radical and M is a member 8. Phenylcyclooctatetraene. of the group consisting of lithium and sodium, in an References Cited in the file of this patent inert atmosphere to obtain a mixture of substituted phenylcyclooctatetraene and organometallic complexes, cooling the reaction products, decomposing the complexes so formed by carbonation, and separating the sub- Cope et al.; Jour. Amer. Chem. Soc., vol. 72 (January 1950), pages 630-1 (2 pages). 

1. THE PROCESS OF PREPARING PHENYLCYCLOOCTATETRAENE WHICH COMPRISES HEATING CYCLOOCTATETRAENE IN A SOLUTION OF A REACTANT OF THE FORMULA RM IN WHICH R IS THE PHENYL RADICAL AND M IS A MEMBER OF THE GROUP CONSISTING OF LITHIUM AND SODIUM IN AN INERT ATMOSPHERE TO OBTAIN A MIXTURE OF PHENYLCYCLOOCTATETRAENE AND ORGANOMETALLIC COMPLESES, COOLING THE REACTION PRODUCTS, DECOMPOSINGG THE COMPLEXES SO FORMED BY HYDROLYSIS, AND SEPARATINGG THE PHENYLCYCLOOCTATRAENE FROM THE OTHER REACTION PRODUCT. 